Adjuvant chemotherapy (CMF) for stage III breast cancer: a randomized trial.

A randomized trial of the effect of adjuvant CMF chemotherapy in patients with Stage III breast cancer receiving primary local radiation or local radiation plus surgery, failed to reveal a survival benefit from early systemic treatment. The subset of premenopausal patients receiving chemotherapy did, however, show a significant prolongation of disease-free survival from 23 to 55 months. Overall survival of this subgroup was not increased. The study included the use of two dose levels of CMF to assess whether higher chemotherapy doses would be more effective. No dose effect was observed. Initial local control with radiation therapy or radiation plus surgery was achieved in the majority (90.9%). Distal recurrence and death from metastatic disease were the major causes of treatment failure. Treatment benefit among premenopausal patients was mainly delayed onset of distal metastatic disease. Among premenopausal patients, salvage therapy for metastatic disease appeared more effective in those not previously exposed to systemic treatment.

Lack of a significant independent effect of race on survival in breast cancer.

In an analysis of 2033 patients with breast cancer from two population groups presenting to the Combined Breast Clinic of the Johannesburg and Hillbrow Hospitals, black patients were found to present with more advanced stage disease (P much less than 0.0001) and to have a poorer prognosis within each stage than whites (P less than 0.005- less than 0.001). Intrastage inhomogeniety was indicated by the finding that black patients had significantly more advanced T and N categories within stage grouping as compared to white patients (P = 0.013-P less than .001). A multivariate analysis controlling for age, T and N in nonmetastatic showed that when these factors were taken into consideration there was no significant independent effect of race on survival. The data indicate that the poorer prognosis which has been previously reported for black patients probably results from intrastage variability of disease bulk, supporting the use of the TNM rather that the stage grouping system for prognostication. Age differences also were evident when the two population groups were compared, with breast cancer in blacks appearing to present at an earlier age. Further analysis showed that these age differences were related to the age structure of the two populations and that breast cancer probably does not occur at a younger age in black subjects. Ethnic origin, does not appear to play a significant independent role in the prognosis of breast cancer in women.

A study of the mantle technique for Hodgkins disease using thermoluminescent dosimetry.

A study of the mantle technique for Hodgkins disease patients was embarked upon using thermoluminescent dosimetry (TLD) and a RANDO phantom. There was concern that the technique using Co-60 and turning the patient over for the posterior field may not be optimal as it was felt that the axillary areas of these patients were being under-dosed. A variety of treatment set-ups were performed on a 60-Cobalt unit at extended SSD. The phantom was planned for treatment lying supine for the anterior field and prone for the posterior field. Measurements were made in the neck, hilum and axillae using various combinations of compensators and lead filters. The combination of full field compensators and a lead filter gave the best results in the phantom but did not give satisfactory axillary readings in the patient situation. This was attributed to the difference in shape and AP separation of the patient when lying prone. RANDO, being solid, retains its shape. Treatment was then planned for a 6 MV linear accelerator using a vertical couch extender which enables the patient to remain supine throughout the treatment by increasing the table height to allow the posterior portal to be treated through the couch. Full field compensation was found to give an adequate dose to all the measured areas. This technique has since been performed on 28 patients being treated for Hodgkins disease at the Hillbrow Hospital, and the average axillary dose recorded in these patients is 88.6% of the prescribed dose.

Breast cancer in men. Clinical features, hormone receptor status, and response to therapy.

Stage, estrogen receptor status, treatment and survival of 29 men with breast cancer attending the Breast Clinic of the Johannesburg Hospital between 1976 and 1985 are reviewed. Most patients had locoregionally advanced disease at presentation. Estrogen receptors (ER) were detected in significant concentration in 15/23 (65%). Local control was achieved in the majority, 19/26 (73%), by either surgery or radiation therapy alone or by combined modality treatment. Fifteen of 23 patients tested (65%) were ER-positive (greater than 10 fmol/mg protein). For patients with metastatic disease hormone receptor status was predictive of response to hormonal manipulation. Tamoxifen was the most acceptable and frequently used form of hormone therapy with 7/12 patients responding. Combination chemotherapy gave a response rate comparable to that seen in women with breast cancer.

Use of aminoglutethimide for the treatment of advanced breast cancer. Clinical correlations with previous treatment, oestrogen-receptor and menstrual status.

In a study of 118 patients with advanced breast cancer treated with aminoglutethimide plus hydrocortisone replacement the overall objective response rate was 42 (36%). Response was not determined either by the nature or the extent of previous treatment, including endocrine therapy and/or chemotherapy, nor by oestrogen-receptor status. The vast majority of patients who responded were postmenopausal but a complete response was seen in a premenopausal patient with skin metastases. Aminoglutethimide is useful in the second-line treatment of postmenopausal subjects with advanced breast cancer.

Late radiation cystitis after treatment for carcinoma of the bladder.

Between 1978 and 1982, 88 patients were treated with radiotherapy at the University of the Witwatersrand Hospitals for carcinoma of the bladder. They were followed up for evidence of cystitis (i.e. frequency, urgency, nocturia, dysuria, haematuria). Those with persistent symptoms underwent cystoscopy. Biopsies were taken of areas suspicious of residual or recurrent tumour. The total incidence of late bladder complications was 11 (12,5%). Of these 11 patients, 6 had persistent or recurrent tumour. The implications of this are discussed.

Pregnancy after radiation therapy for carcinoma of the cervix.

A successful pregnancy after intracavitary radiation therapy for carcinoma of the cervix is described. An additional 13 similar cases from the literature are reviewed. The possible reasons for the occurrence of these pregnancies despite irradiation to the ovaries, cervical canal and endometrium are discussed. The fact is emphasized that no genetic damage to the child was expected.

Treatment of advanced breast cancer with aminoglutethimide--response after previous tamoxifen treatment.

Thirty-one postmenopausal patients with advanced breast cancer either unresponsive to tamoxifen or progressing after responding to tamoxifen were treated with aminoglutethimide (1 000 - 1 250 mg/d) plus hydrocortisone replacement. The response rate was 33% in patients who had never responded to tamoxifen and 47% in patients who had previously responded to tamoxifen. The overall response rate was 42%. These results show that aminoglutethimide is an effective second-line hormonal treatment for patients with advanced breast cancer.

High-dose weekly fractionation radiotherapy in advanced cancer of the uterine cervix.

A trial comparing two different radiotherapy techniques and schedules in the treatment of 83 patients with advanced cancer of the uterine cervix (stage IIIB) employing external irradiation alone is described. The one technique, used routinely in this department, employed a conventional daily fractionation schedule while the other used a high-dose weekly fractionation regimen. The techniques are described. The aim of the trial was to compare the efficacy and morbidity of these two methods of treatment. Dose distribution curves in cross-section and midsagittal planes are shown and calculations or equivalent doses at various selected points using Ellis's nominal single-dose formula are tabulated. The 2-year survival figures were 33% for the daily fractionation technique and 22% for the weekly regimen. Serious late complication rates were 6% for the daily regimen and 22% for the weekly schedule. These differences are not statistically significant. Late complication rates in the weekly fractionation regimen appeared to be lower than figures quoted by other authors. Local control within the irradiated volume was better in the group treated by the daily fractionation method.

Germ cell tumours of the ovary. A clinical study of 15 cases.

Our experience with germ cell tumours of the ovary is reviewed. Over the last 10 years, 15 cases, representing 6,4% of all our referred patients with malignant ovarian tumours, have been analysed. The type of tumour, histological appearances, stage, treatment and results of treatment are presented. The tumour most commonly seen was the dysgerminoma, comprising 60% of all cases (9 patients). Multimodal treatment generally consisted of surgery and radiotherapy for dysgerminoma with the addition of chemotherapy for the non-dysgerminomas. Survival depends on the stage and histological appearances of the tumour. Patients in whom the disease is at advanced stages have a poor prognosis, irrespective of histological features. A general review of this subject is also given.

Radiotherapy and surgery in the management of stage IB and IIA carcinoma of the cervix.

Ninety-two consecutive patients with stages IB and IIA carcinoma of the cervix were treated by one of two regimens: pre-operative intracavitary caesium-137 followed by a Wertheim hysterectomy (group 1) or staging laparotomy with biopsy of suspicious lymph nodes (group 2) (if there was no evidence of tumour on examination of a frozen section of the lymph nodes a Wertheim hysterectomy was performed, but if a tumour was present the abdomen was closed and a course of radical irradiation given). When there was evidence of extracervical spread on examination of the specimen after the Wertheim hysterectomy, postoperative irradiation was given. It was found that clinical staging had been incorrect in 38,5% of patients thought to have stage IB disease and in 71,4% of those thought to have stage IIA disease. The actuarial survival curves showed no significant statistical difference between group 1 and group 2. When examination of the operative specimen showed tumour invasion of the parametrium only, the disease was well controlled by postoperative irradiation (all 7 such patients survived). On the other hand, when there was evidence of tumour invasion of pelvic lymph nodes the 4-year survival rate fell to 31% (4 out of 13 patients), despite the use of postoperative irradiation.

Total lymphoid irradiation in kidney and liver transplantation in the baboon: prolonged graft survival and alterations in T cell subsets with low cumulative dose regimens.

Prolonged kidney and liver allograft survival was produced in baboons by low cumulative doses (500 to 1200 rad) of total lymphoid irradiation (TLI). Continuing normal graft function for more than 1 yr after transplantation was seen in 10 animals in this series. The longest survivor (greater than 4 years) rejected a third party kidney allograft in typically acute fashion 1 yr after the original transplantation. The dose-response effect was parabolic, with a cumulative dose of 800 rad given as twice weekly fractions of 100 rad each being the most effective. With smaller cumulative doses (500 or 600 rad) results were improved if TLI was administered as a larger number of smaller fractions. These regimens are free of the radiation related mortality observed in earlier studies with larger cumulative doses. As in previous studies, the injection of donor bone marrow was not essential for prolonged and continuing graft survival. The field irradiated was extensive, and included a substantial part of the of the hemopoietic bone. Restricting the field irradiated to that approximating what is used clinically in patients with Hodgkin's disease resulted in markedly poorer graft survival. Alterations in T cell subpopulations were studied in these baboons with the use of the anti-human monoclonal antibodies OKT11 (anti-total T cells), OKT4 (anti-T helper cells; Th), and OKT8 (anti-T suppressor/cytotoxic cells, Tsc), which cross-react with baboon lymphocytes. After completion of TLI but before transplantation, the relative percentage of Tsc cells fell and the percentage of Th and the Th/Tsc ratio rose. Transplantation was followed by an inversion of this ratio due to reciprocal changes in the percentages of Th and Tsc cells. This pattern persisted and increased until 6 mo after transplantation, when it reverted to that seen in untreated control animals. This was maintained in long surviving animals up to 17 mo after transplantation. Transplantation was also followed by a marked early increase in the percentage of Ia+ (OKIa1 anti-human monoclonal antibody) total T, T4+, and T8+ cells. If findings in the human, in which activated suppressor but no cytotoxic T cells are Ia+, can be extrapolated to the baboon, a possible explanation for the serial changes observed in the present studies may be that transplantation after TLI results in a polyclonal expansion of nonspecific suppressor T cells. These disappear with time leaving specific suppressor T cells that may be responsible for continuing graft acceptance. Formal proof of this hypothesis will require appropriate functional studies.

Late metastases of ovarian carcinoma. A case report.

In cases of ovarian carcinoma distant metastases are rarely discovered before local spread has become evident. This article reports an unusual case in which renal metastases appeared 9 years after the initial diagnosis of epithelial ovarian carcinoma. A discussion of the histological features of the tumour and the spread of ovarian carcinoma is included.